A fundamental tenet of cancer chemotherapy is that the "curability" of a neoplasm is dependent upon the number of viable cells present at the start of therapy. Therefore any intervention which would reduce the total tumor burden initiation of chemotherapy would be efficacious. The role of blood platelets and the coagulation mechanism in the hematogenous spread of malignant disease is presently unclear. The use of anticoagulant therapy has been less than satisfactory probably due to lack of specificity of the agents used. Prostacyclin (PGI2) is the most potent antithrombogenic agent known. Preliminary results demonstrate its effectiveness against metastasis of B16 melanoma and Lewis Lung carcinoma cells. The proposed research will utilize in vivo and in vitro methods to demonstrate that tumor cell alteration in normal endothelial cell prostacyclin production could explain subsequent adhesion and thrombi formation. Prostacyclin is proposed as a potent antimetastatic agent whose effectiveness may be demonstrated even after tumor cell attachment effecting a "flushing" of tumor cells from capillary beds. 125I Udr labelled tumor cells and scanning E.M. will be used to evaluate the role of prostacyclin in tumor cell-endothelial interactions. Isolated bovine endothelial cells will be used to determine if tumor cells can decrease PGI2 synthesis. A specific PGI2 synthetase inhibitor and a drug known to increase PGI2 synthesis will be used to evaluate whole animal PGI2 status upon spontaneous metastasis from subcutaneous tumors. The proposed research is expected to yield important data concerning the efficacy of a potentially powerful adjuvant to conventional cancer surgery and chemotherapy.